NEW YORK (GenomeWeb) – Alnylam Pharmaceuticals this week announced the upcoming release of clinical data on a number of its RNAi drug candidates including ones from its flagship TTR-mediated amyloidosis (ATTR) programs, as well as ones for hemophilia, complement-mediated diseases, and hypercholesterolemia.
The company, which also posted its fourth quarter 2014 financial results, further disclosed that it aims to begin human studies for its hepatic porphyria treatment ALN-AS1 and to select a development candidate for its program in primary hyperoxaluria type 1 (PH1).
Alnylam's most advanced agent is patisiran, which comprises siRNAs designed to inhibit the gene TTR, which is mutated in ATTR and triggers the production of abnormal amyloid proteins. The drug candidate is formulated in lipid nanoparticles (LNPs) licensed from Tekmira Pharmaceuticals and entered Phase III testing in late 2013 for a form of the disease called familial amyloidotic polyneuropathy.
This week, Alnylam said that it aims to present 12-month data from an open-label extension study that enrolled patients from a now-complete Phase II trial in April at the American Academy of Neurology's 67th Annual Meeting. The company previously released data showing that multiple doses of the drug triggered rapid, dose-dependent, and durable knockdown of serum TTR levels.
Although Alnylam once relied heavily on Tekmira's LNPs, the companies went through a bitter legal battle over intellectual property related to the delivery technology several years ago. Alnylam has since shifted its attention to a proprietary conjugate delivery approach called GalNAc that relies on targeting the asialoglycoprotein receptors expressed on the surface of hepatocytes for liver delivery and enables subcutaneous drug administration.
Alnylam developed a subcutaneous version of patisiran called revusiran using the GalNAc approach, and in November presented Phase II data showing that the compound could knock down levels of its target protein by as much as 98.2 percent in patients with a form of ATTR called familial amyloidotic cardiomyopathy.
This week, Alnylam said that it will release additional data from that trial at the American College of Cardiology 64th Annual Scientific Session & Expo in March. Revusiran is currently in Phase III testing.
Alnylam said that it is also planning to present new Phase I data on its hemophilia and bleeding disorder drug ALN-AT3 sometime in the first half of this year.
The agent is the first to feature an optimized version of the company's GalNAc conjugate delivery technology, dubbed enhanced stabilization chemistry, which is expected to replace standard GalNAc conjugates in future Alnylam programs, and targets antithrombin, an endogenous inhibitor of thrombin generation.
In late 2014, Alnylam released Phase I data showing that ALN-AT3 could durably suppress its target by as much as 57 percent at low microgram per kilogram doses in healthy volunteers.
Also in the first half of 2015, Alnylam aims to release initial data from a Phase I/II trial of its complement-mediated disease treatment ALN-CC5 that kicked off earlier this month, as well as data from a recently initiated Phase I trial of its GalNAc-enabled hypercholesterolemia treatment ALN-PCSsc. Both drugs use the GalNAc technology.
As for its preclinical initiatives, Alnylam said that it will move the GalNAc-enabled ALN-AS1 into Phase I for hepatic porphyrias, a collection of inherited disorders caused by deficiencies in liver enzymes involved in the biosynthesis of heme, a component of hemoglobin, by this summer.
The company also plans to select a formal development candidate for its program in PH1, a rare kidney disease, in the first half of the year.
Fourth quarter financials
For the three-month period ended Dec., 31, 2014, Alnylam reported a net loss of $21.4 million, or $.28 a share, versus a year-ago loss of $32.4 million, or $.51 a share.
Revenues in the quarter jumped to $24 million from $10.8 million a year earlier, and included $8.8 million from partner Monsanto, $6.9 million from partner The Medicines Company, and $5.5 million from an alliance with Takeda Pharmaceuticals.
Alnylam's research and development costs climbed to $55.5 million from $32.1 million, while general and administrative spending increased to $14.2 million from $8.3 million.
At the end of 2014, Alnylam had cash, cash equivalents, and marketable securities totaling $881.9 million. This does not include the proceeds of a January public offering that netted nearly $500 million.
The company said that it expects to end 2015 with more than $1.2 billion in cash, cash equivalents, and marketable securities.